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M. Suarez et al. / Tetrahedron 62 (2006) 1365–1371
1370
(C30, C50), 128.5 (C40), 127.5 (C20, C60), 107.6 (C6), 106.6
(C4a), 60.2 (OCH2), 52.2 (OCH3), 40.2 (C5), 17.9 (CH3),
13.9 (CH3); MSEI m/z (%): 385 ([MKHCl]%C, 16), 356
(29), 312 (25), 250 (100), 223 (37), 195 (25). Anal. Calcd
for C19H20ClN3O4S (421.90): C: 54.09; H: 4.78; N: 9.96; S:
7.60. Found: C: 53.87; H:4.75; N: 10.07; S: 7.59.
4.4.6. 6-Methoxycarbonyl-5-(4-metoxycarbonylphenyl)-
7-methyl-5,8-dihydro-2H-pyrido[3,2-e][1,3]thiazin-2-
iminium chloride (8g). Prepared from methyl 6-chloro-4-
(40-methoxycarbonylphenyl)-5-formyl-2-methyl-1,4-di-
hydropyridine-3-carboxylate (2g). Yield 52%; mp 242–
244 8C; IR (KBr) nmax 33890 and 3255 (nNH), 1725 and
1690 (nC]O), 1647 (nC]N) cmK1; 1H NMR (DMSO-d6)
d: 12.76 (1H, s, NH), 10.64 (1H, s, 0NH),010.35 (1H, s, NH),
8.45 (1H, s, H4), 7.89 (2H, d, H3 , H5 , JZ8.4 Hz), 7.42
(2H, d, H20, H40, JZ8.4 Hz), 5.16 (1H, s, H5), 3.81 (3H, s,
OCH3), 3.56 (3H, s, OCH3, overlaping with de H2O signal),
2.42 (3H, s, CH3); 13C NMR (DMSO-d6) d: 167.5 (C8a),
166.5 (C4), 165.9 (COO), 165.8 0(COO), 155.5 (C2), 150.8
(C10), 144.2 (C7), 129.9 (C30, C5 ), 128.5 (C40), 127.3 (C20,
C60), 107.2 (C6), 106.6 (C4a), 52.1 (OCH3), 51.5 (OCH3),
4.4.3. 6-Methoxycarbonyl-7-methyl-5-phenyl-5,8-di-
hydro-2H-pyrido[3,2-e][1,3]thiazin-2-iminium chloride
(8d). Prepared from methyl 6-chloro-4-phenyl-5-formyl-2-
methyl-1,4-dihydropyridine-3-carboxylate (2d). Yield,
73%; mp 241–243 8C; IR (KBr) nmax 3360 and 3220
(nNH), 1690 (nC]O), 1645 (nC]N) cmK1 1H NMR
;
(DMSO-d6) d: 12.61 (1H, s, NH), 10.57 (1H, s, NH), 10.32
(1H, s, NH), 8.45 (1H, s, H4), 7.35–7.22 (5H, m, Ph), 5.06
(1H, s, H5), 3.58 (3H, s, OCH3); 2.43 (3H, s, CH3); 13C
NMR (DMSO-d6) d 167.3 (C8a), 166.4 (C4), 166.0 (COO),
155.3 (C2), 145.9 0(C10), 143.5 (C7), 129.0 (C20, C60), 127.3
(C40), 126.7 (C3 , C50), 108.0 (C6), 107.4 (C4a), 51.5
(OCH3), 39.7 (C5), 17.8 (CH3); MSEI m/z (%): 313
([MKHCl]%C, 21); 298 (17), 236 (100), 209 (62), 177 (8).
Anal. Calcd for C16H16ClN3O2S (349.84): C: 54.93; H:
4.61; N: 12.01; S: 9.17. Found: C: 54.87; H: 4.65; N: 12.03;
S: 9.19.
39.1 (C5), 17.9 (CH3); MSEI m/z (%): 371 ([MKHCl]%C
,
16); 356 (25), 236 (100), 209 (62), 177 (8). Anal. Calcd for
C18H17ClN3O4S (406.06): C: 53.14; H: 4.21; N: 10.33; S:
7.88. Found: C: 53.01; H: 4.17; N: 10.42; S: 7.89.
Acknowledgements
Supports of this work by Proyectos Alma Mater (CUBA)
and MEC of Spain (PQU2002-00855 and CTQ2004-03760)
4.4.4. 5-(2-Chlorophenyl)-6-methoxycarbonyl-7-methyl-
5,8-dihydro-2H-pyrido[3,2-e][1,3]thiazin-2-iminium
chloride (8e). Prepared from methyl 6-chloro-4-(2-chloro-
phenyl)-5-formyl-2-methyl-1,4-dihydropyridine-3-carbo-
xylate (2e). Yield 69%; mp 304–306 8C; IR (KBr) nmax 3370
´
are gratefully acknowledged. M. Suarez is grateful to
SAB2003-0161 from Secretarıa de Estado de Universidades
´
´
´
e Investigacion del Ministerio de Educacion y Ciencia de
Espan˜a. H. Novoa is indebted to the Postdoctoral Mandate
fellowship of the Research Funds/Onderzoeksfunds, K.U.
Leuven (Belgium).
1
and 3225 (nNH), 1692 (nC]O), 1648 (nC]N) cmK1; H
NMR (DMSO-d6) d: 12.68 (1H, s, NH), 10.58 (1H, s, NH),
10.35 (1H, s, NH), 8.15 (1H,0 s, H4), 7.44 (1H, m, H30),
7.33–7.24 (3H, m, H50, H40,H6 ), 5.50 (1H, s, H5), 3.51 (3H,
s, OCH3); 2.40 (3H, s, CH3); 13C NMR (DMSO-d6) d 167.1
(C8a), 165.7 (COO), 1605.3 (C4), 155.9 (C2), 144.3 (C7),
142.9 (C10), 130.80 (C2 ), 130.7 (C60), 129.9 (C30), 129.1
(C40), 128.2 (C50), 107.3 (C6), 106.6 (C4a), 51.4 (OCH2),
37.3 (C5), 17.9 (CH3); MSEI m/z (%): 347/349
([MKHCl]%C, 14/6); 332/334 (25/9), 288/290 (21/8), 236
(100), 209 (61), 177 (9). Anal. Calcd for C16H15Cl2N3O2S
(384.28): C: 50.01; H: 3.93; N: 10.93; S: 8.34. Found: C:
49.83; H: 3.92; N: 11.00; S: 8.32.
Supplementary data
Supplementary data associated with this article can be
054. The main geometrical characteristics of compounds
8b–g obtained from B3LYP/6-31G*24 ab initio are collected
in the supplementary material.
4.4.5. 6-Methoxycarbonyl-7-methyl-5-(30-nitrophenyl)-
5,8-dihydro-2H-pyrido[3,2-e][1,3]thiazin-2-iminium
chloride (8f). Prepared from methyl 6-chloro-4-(3-nitro-
phenyl)-5-formyl-2-methyl-1,4-dihydropyridine-3-car-
boxylate (2f). Yield 58%; mp 250–252 8C; IR (KBr) nmax
3390 and 3255 (nNH), 1690 (nC]O), 1645 (nC]N), 1535
and 1350 (nNO2) cmK1; 1H NMR (DMSO-d6) d 12.70 (1H,
s, NH), 10.64 (1H, s, NH), 10.38 (1H, s, NH), 8.52 (1H, s,
H4), 8.13 (1H, t, H20, JZ1.8 Hz), 8.09 (1H, ddd, H40, JZ
7.9, 1.8, 1.0 Hz), 7.73 (1H, dt, H60, JZ7.9, 1.0 Hz), 7.62
(1H, t, H50, JZ7.9 Hz), 5.28 (1H, s, H5), 3.57 (3H, m,
OCH3), 2.45 (3H, s, CH3); 13C NMR (DMSO-d6) d 167.6
(C8a), 166.7 (C4), 165.8 (COO), 155.6 (C2), 1480.1 (C30),
147.6 (C10), 144.7 (C7), 133.9 (C20), 130.6 (C4 ), 122.3
(C60), 121.6 (C50), 106.9 (C6), 106.4 (C4a), 51.6 (OCH3),
References and notes
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4994569, 1991.
2. Koketsu, M.; Tanaka, K.; Takenaka, Y.; Kwong, C. D.;
Ishihara, H. Eur. J. Pharm. Sci. 2002, 15, 307–310.
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5. Malinka, W.; Kaczmarz, M.; Filipek, B.; Sepa, J.; Gold, B. Il
Farmaco 2002, 57, 737–746.
39.3 (C5), 18.0 (CH3); MSEI m/z (%): 358 ([MKHCl]%C
,
6. (a) Janis, R. A.; Silver, P. J.; Triggle, D. J. Adv. Drug Res.
1987, 16, 309–391. (b) Bossert, F.; Vater, W. Med. Res. Rev.
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Chem., Int. Ed. Engl. 1991, 30, 1559–1578.
13); 341 (22), 236 (100), 209 (61), 177 (9). Anal. Calcd for
C16H15ClN4O4S (394.83): C: 48.67; H: 3.83; N: 14.19; S:
8.12. Found: C: 48.56; H: 3.89; N: 14.22; S: 8.15.